The present invention relates to a 6-O-methylerythromycin A derivative which is useful as an intermediate for preparation of 6-O-methylerythromycin A and useful as an antibacterial agent.
U.S. Pat. No. 4,331,803 discloses a method for synthesis of 6-O-methylerythromycin A which is extremely useful as an antibacterial agent.
In this method, 2'-O,3'-N-bis(benzyloxycarbonyl)-N-demethylerythromycin A derived from erythromycin A is subjected, in turn, to methylation of a hydroxy group at the 6-position using methyl iodide and sodium hydride, to elimination of benzyloxycarbonyl groups at the 2'- and 3'-positions and to N-methylation under reductive conditions to give 6-O-methylerythromycin A.
However, this method lacks a high selective methylation of a hydroxy group at the 6-position and produces not a little 11-O-methyl form as major by-product. Therefore, there are drawbacks of causing low preparation yield of the objective 6-O-methylerythromycin A and causing complication in purification procedure.
As a result of the studies to decrease the formation of the by-products and to synthesize 6-O-methylerythromycin A efficiently, the present inventors have found the facts that methylation of 2'-O,3'-N-bis(benzyloxycarbonyl)-N-demethylerythromycin A, in which carbonyl group at the 9-position is modified by a substituted or unsubstituted benzyloxyimino group, takes place selectively at a hydroxy group at the 6-position to give a 6-O-methyl form in good yield, and that 6-O-methylerythromycin A 9-oxime, obtained by elimination of benzyloxycarbonyl group and substituted or unsubstituted benzyl group and by N-methylation of the 6-O-methyl form, can be easily converted to 6-O-methylerythromycin A by deoximation and this oxime form itself is a novel antibiotic having a strong antibacterial activity, and thus the present invention has been completed.